DNA double helix
Nucleus 3D
Nucleus 3D labeled
The cell nucleus is the command and control centre of the cell. It is essentially a minute computer which stores
instructions in the form of DNA (deoxyribonucleic acid or deoxyribose nucleic acid). DNA is a superb information
storage medium - a memory stick based on DNA instead of silicon could probably store the entire Internet with
ease! (At least it can according to my calculations). The nucleus is the largest organelle in an animal cell. In
mammals it's average diameter is about 6 micrometres. It is typically spherical or ellipsoidal, but may have more
complicated shapes in some cell types. It is enclosed in a double
unit membrane - the nuclear envelope (NE).
the nuclear envelope is continuous with the
endoplasmic reticulum (ER).
The nuclear envelope encloses the nuceloplasm. The nucleoplasm is mostly occupied by chromatin. Each
chromosome consists of a single DNA molecule coiled around proteins called
histones. This DNA/protein
complex forms a fine fibrous material called chromatin. Especially dense regions of chromatin, in which the
DNA is highly coiled, are called
heterochromatin, whilst less dense chromatin, in which the DNA is largely
uncoiled from the protein scaffold, is called
euchromatin. Within the nucleus are one or more dense regions
called nucleoli (singular = nucleolus).

The function of the
nucleolus is to synthesise ribosomal RNA and to assemble ribosomes. The nuclear
envelope is perforated by pores called
nuclear pores. The nuclear pores allow materials to enter and exit
the nucleus and each is guarded by a nuclear pore complex, made-up of many proteins. For example, the
nuclear pore complex will export mRNA, synthesised in the nucleus, into the cytoplasm. It will export
completed ribosomes into the cytoplasm and import proteins and raw materials that the nucleus needs.

The DNA stores information that serves several main functions:
  1. Coding for proteins, which are the building blocks of the cell - DNA is like a blueprint of all the
    proteins the cell can make. A stretch of DNA coding for one polypeptide or protein is called a gene.
  2. Coding for RNA (ribonucleic acid) - RNA forms several important enzymes (called ribozymes)
    including the ribosome active sites and various other RNA molecules whose functions are just
    beginning to be understood.
  3. Regulatory DNA - switches genes on and off in response to signals from the cell - this is the
    equivalent of the computer's CPU - it takes inputs and computes the relevant output.
  4. Structural DNA - some DNA may possibly serve to position other elements and to fold around or bind
    to the protein scaffold.
  5. 'Junk DNA' - DNA with no known function. Some of this DNA consists of defective and inoperable
    genes, called pseudogenes or dead genes - relics of evolution. Some of this DNA is of viral origin -
    many viruses will insert their own parasitic DNA into the host cell DNA. Sometimes this viral DNA may
    mutate and become useless or indeed useful to the cell. In this way viruses can accelerate evolution.
    Estimates vary, but at least 8% of the human genome is thought to be of viral origin! Some junk DNA
    may have functions not yet determined.

The nucleus of a human cell stores 33 Gb (33 gigabases) or about 10 gigacodons of information - it is
approximately equivalent in storage capacity to a computer DVD but is so much smaller!
Cell nucleus showing additional structures
The diagram above illustrates some additional structures found inside the nucleus. Inside the nuclear envelope
is a network of protein fibres called the
nuclear lamina, made of the protein laminin. The nuclear lamina is part of
the cytoskeleton and supports the nuclear membrane. Cajal bodies are 0.1-2 micrometres in diameter and
number 1-10 per nucleus and they are involved in the manufacture of certain specialised RNA molecules. The
function of the PML bodies is unknown. Each chromosome territory corresponds to the region occupied by the
chromatin of a single chromosome. In a human body cell there are 46 chromosomes (23 pairs, 23 paternal and
23 maternal).
The Genetic code

DNA is a double helix – that is a molecule of DNA consists of two helical strands wound together.
Each of these strands is a polymer of
nucleotides and the two strands are connected to one another
by bonds (
hydrogen bonds) which are much like the rungs of a ladder. Nucleotides within each strand
are joined by covalent phosphodiester bonds (-O-P-O-) in a condensation reaction.
An electron micrograph of a section through an animal cell nucleus (from an insect cell) showing
heterochromatin (H), euchromatin (E) and the nucleolus with its fibrous centre (FC) and peripheral
fibrous region (PF).
Nucleus
Each nucleotide subunit is made of a modified ribose sugar molecule (called deoxyribose as it has
lost an oxygen) joined to a phosphate group and one of four bases (adenine, A; guanine, G; cytosine,
C; and thymine, T). In the double helix, each base pairs up with another base to form a base pair (bp).
A always pairs with T and C with G.
These four bases are the ‘letters’ of the genetic code. These letters make up ‘words’ each of which
is three nucleotides (or 3 bases) long – a single ‘word’ codes for one of about 20 different amino
acids. Each such 'word' is called a
codon.

These ‘words’ are grouped into ‘sentences’ or
genes, each of which encodes the sequence of amino
acids that  make up a single protein (proteins are made of amino acids!).

One strand of the DNA molecule will contain the necessary code for the proteins the cell needs to
make, this is the sense strand (
coding strand), the other strand is complementary to the sense
strand (the antisense or non-coding strand).

Cytosine and thymine are single ring molecules, guanine and adenine are double-rings and these
rings all contain nitrogen (N). Ribose and deoxyribose are 5C monosaccharide sugars. Thus, DNA
contains the elements C, H, O, N and P (but NOT S).
The sequence of nucleotides (or equivalently bases) in DNA  encodes vital information to the cell. Some parts of the DNA
are structural, in which case the nucleotide sequence determines the 3D structure of the DNA molecule. Other parts of
the DNA carry the instructions needed to make
RNA (ribonucleic acid). This RNA may be ribosomal RNA (rRNA), one of
the components of ribosomes or enzymatic RNA (ribozymes) or messenger RNA (mRNA) which carries instructions for
protein synthesis. Each mRNA carries the instructions to make a polypeptide (usually one polypeptide in eukaryotes,
possibly more in prokaryotes and viruses). One definition of a gene is that it is a region of DNA that encodes a single
polypeptide (the 'one gene - one polypeptide' hypothesis). Specifically, for a given gene, the information is coded for on
one strand of the DNA, called the
sense or coding strand. The other complimentary strand is then the non-coding or
antisense strand (note that scientists disagree over the definition of sense and antisense strands).

The Genetic Code in detail

So, we can think of a gene as a code for one polypeptide. Polypeptides are made of amino acids (see protein structure)
and the number and order or sequence of the 20 different types of amino acid that make proteins must be coded for in
the DNA so that the polypeptide contains the right amino acid in a given place. [Actually, there are more than 20 amino
acids, but some of these are modified versions of the 20 core amino acids that have been chemically modified in the
cytosol). The names of these amino acids, and their abbreviations, are given below:
The genetic code is made up of 'words' called codons, each codon is three bases/nucleotides in length. Thus, the
bases/nucleotides are 'letters', the codons are 'words' and the gene is a 'sentence' metaphorically speaking.

Note that the word codon, specifically refers to the words of the genetic code once they have been copied or transcribed
onto an intermediate messenger molecule called
messenger RNA (mRNA) - see ribosomes and protein synthesis for
details. However, codons can also be used to refer to the equivalent code on the coding strand of the DNA (for want of a
better word). [The differences are that the sequence on the DNA coding strand will be complimentary to that on the
mRNA, which is why there is disagreement about which strand should be considered the coding strand, and also in RNA
the base T is replaced by uracil, U). Consider the questions and their answers below, to check your understanding:
Where in Q.2 we have defined the coding strand of the DNA molecule to be that strand which the RNA polymerase reads during
transcription. [Splicing is a process in which some of the DNA is omitted from the mRNA copied from it]. See ribosomes and the
structure of RNA for a more complete explanation.

To fully understand the genetic code it is necessary to understand how the
ribosomes accomplish protein synthesis.
NPC (Nuclear pore Complex) - sideview
NPC - sideview in section, showing outer and inner
nuclear membranes (in blue); cytoplasm above,
nucleoplasm below
NPC (Nuclear pore Complex) - sideview in
section
NPC - view from 'above' (from
cytoplasmic side)
NPC - view from 'below' (from nuclear
side)
Above: a 3D model of the nuclear pore complex (NPC).
The NPC is more than a simple molecular sieve, it is a
mechanism that transports selected materials into and out
of the nucleus in a regulated manner. The structure is
made of about 100 proteins (in mammals, about 30 in
yeast) and is about 40 nm in diameter. This structure is a
remarkable (and complex) molecular nano-machine. Click
images to enlarge.